The overall goal of this program is to provide information on early phases of vertebrate CNS development. The first focus of the program is the role of secreted factors in the induction and patterning of cells in the mammalian nervous system. In Project I, Dr. Dodd will examine the role of sonic hedgehog and members of the TGFbeta and FGF families of protein growth factors in the generation of central midline cells at different raustro-caudal levels of the neuraxis. In Project II, Dr. Mason will use neuroanatomical approaches to examine cell fate and specification in the ventral diencephalon and optic chaism. In Project III, Dr. Jessel will use molecular genetic techniques to assess the role of TGFbeta-like factors in the generation of dorsal neural cell types in mouse embryos. These studies will focus on the function of GDF7, BMP6 and BMP7, each of which is expressed by roof plate cells at the dorsal midline of the embryonic CNS. A second focus of the program is the control of the cerebellar development. In Project IV, Dr. Hatten will use molecular approaches to examine early steps in the specification of granule neuron progenitors within the rhombic lip, examining the role of BMP6, BMP7 and GDF7 in expression of granule cell markers. In Project V, Dr. Heintz will use molecular biological approaches to define the regulation of the zinc finger transcription factor RU49, a granule cell marker, and the brain lipid binding protein BLBP, as well as novel genes that show regulated expression during cerebellar histogenesis. In Project VI, Dr. Joyner will examine the genetic control of cerebellar patterning using the En-2 gene as a genetic entry point.